全文获取类型
收费全文 | 270篇 |
免费 | 18篇 |
出版年
2021年 | 2篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 6篇 |
2014年 | 5篇 |
2013年 | 8篇 |
2012年 | 14篇 |
2011年 | 18篇 |
2010年 | 11篇 |
2009年 | 6篇 |
2008年 | 19篇 |
2007年 | 28篇 |
2006年 | 11篇 |
2005年 | 20篇 |
2004年 | 16篇 |
2003年 | 16篇 |
2002年 | 17篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 4篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1963年 | 2篇 |
1960年 | 1篇 |
1959年 | 1篇 |
1957年 | 2篇 |
1956年 | 2篇 |
1954年 | 3篇 |
1939年 | 1篇 |
排序方式: 共有288条查询结果,搜索用时 16 毫秒
91.
92.
93.
94.
95.
Vasyl A. Ivashov Guenther Zellnig Karlheinz Grillitsch Guenther Daum 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(6):1158-1166
In yeast like in many other eukaryotes, fatty acids are stored in the biologically inert form of triacylglycerols (TG) and steryl esters (SE) as energy reserve and/or as membrane building blocks. In the present study, we identified gene products catalyzing formation of TG and SE in the methylotrophic yeast Pichia pastoris. Based on sequence homologies to Saccharomyces cerevisiae, the two diacylglycerol acyltransferases Dga1p and Lro1p and one acyl CoA:sterol acyltransferase Are2p from P. pastoris were identified. Mutants bearing single and multiple deletions of the respective genes were analyzed for their growth phenotype, lipid composition and the ability to form lipid droplets. Our results indicate that the above mentioned gene products are most likely responsible for the entire TG and SE synthesis in P. pastoris. Lro1p which has low fatty acid substrate specificity in vivo is the major TG synthase in this yeast, whereas Dga1p contributes less to TG synthesis although with some preference to utilize polyunsaturated fatty acids as substrates. In contrast to S. cerevisiae, Are2p is the only SE synthase in P. pastoris. Also this enzyme exhibits some preference for certain fatty acids as judged from the fatty acid profile of SE compared to bulk lipids. Most interestingly, TG formation in P. pastoris is indispensable for lipid droplet biogenesis. The small amount of SE synthesized by Are2p in a dga1?lro1? double deletion mutant is insufficient to initiate the formation of the storage organelle. In summary, our data provide a first insight into the molecular machinery of non-polar lipid synthesis and storage in P. pastoris and demonstrate specific features of this machinery in comparison to other eukaryotic cells, especially S. cerevisiae. 相似文献
96.
All eukaryotes including the yeast contain a lipid storage compartment which is named lipid particle, lipid droplet or oil
body. Lipids accumulating in this subcellular fraction serve as a depot of energy and building blocks for membrane lipid synthesis.
In the yeast, the major storage lipids are triacylglycerols (TGs) and steryl esters (SEs). An important step in the life cycle
of these non-polar lipids is their mobilization from their site of storage and channeling of their degradation components
to the appropriate metabolic pathways. A key step in this mobilization process is hydrolysis of TG and SE which is accomplished
by lipases and hydrolases. In this review, we describe our recent knowledge of TG lipases from the yeast based on biochemical,
molecular biological and cell biological information. We report about recent findings addressing the versatile role of TG
lipases in lipid metabolism, and discuss non-polar lipid homeostasis and its newly discovered links to various cell biological
processes in the yeast. 相似文献
97.
Katrin Fink Hans-J?rg Busch Natascha Bourgeois Meike Schwarz Dennis Wolf Andreas Zirlik Karlheinz Peter Christoph Bode Constantin von zur Muhlen 《PloS one》2013,8(2)
Objective
The endothelial protein C-receptor (EPCR) is an endothelial transmembrane protein that binds protein C and activated protein C (APC) with equal affinity, thereby facilitating APC formation. APC has anticoagulant, antiapoptotic and antiinflammatory properties. Soluble EPCR, released by the endothelium, may bind activated neutrophils, thereby modulating cell adhesion. EPCR is therefore considered as a possible link between the anticoagulant properties of protein C and the inflammatory response of neutrophils. In the present study, we aimed to provide proof of concept for a direct binding of EPCR to the β2 –integrin Mac-1 on monocytic cells under static and physiological flow conditions.Measurements and Main Results
Under static conditions, human monocytes bind soluble EPCR in a concentration dependent manner, as demonstrated by flow cytometry. Binding can be inhibited by specific antibodies (anti-EPCR and anti-Mac-1). Specific binding was confirmed by a static adhesion assay, where a transfected Mac-1 expressing CHO cell line (Mac-1+ cells) bound significantly more recombinant EPCR compared to Mac-1+ cells blocked by anti-Mac-1-antibody and native CHO cells. Under physiological flow conditions, monocyte binding to the endothelium could be significantly blocked by both, anti-EPCR and anti-Mac-1 antibodies in a dynamic adhesion assay at physiological flow conditions. Pre-treatment of endothelial cells with APC (drotrecogin alfa) diminished monocyte adhesion significantly in a comparable extent to anti-EPCR.Conclusions
In the present study, we demonstrate a direct binding of Mac-1 on monocytes to the endothelial protein C receptor under static and flow conditions. This binding suggests a link between the protein C anticoagulant pathway and inflammation at the endothelium side, such as in acute vascular inflammation or septicaemia. 相似文献98.
Hans-Christian Böttcher Marion Graf Karlheinz Sünkel Hartmut Krüger 《Inorganica chimica acta》2011,370(1):523-525
A new convenient high-yield synthesis of the tris-cyclometalated complexes fac-[Rh(ppy)3] (4; ppy = 2-phenylpyridinato) was developed. Complex 4 was prepared in a kind of one-pot synthesis starting from in situ prepared [Rh(acac)(coe)2] (2) which was heated in refluxing 2-phenylpyridine for a short time. After purification by filtration over alumina, compound 4 was obtained in yields of 65%. Also [Rh(acac)(ppy)2] (3) was prepared in a similar manner by oxidative addition of Hppy in refluxing toluene in high yields. In contrast to previous findings with the analogous iridium compounds, there was not any hint at the formation of the isomer mer-[Rh(ppy)3] using similar reaction conditions as applied for iridium. Furthermore the compound [{Rh(μ-Cl)(ppy)2}2] (5) was prepared from [{Rh(μ-Cl)(coe)2}2] (1) and Hppy in refluxing toluene in nearly quantitative yield. 相似文献
99.
The synthesis of bis-cyclometalated [Ir(ptpy)2(gly-gly-OEt)] (2, ptpy = 2-(p-tolyl)pyridinato; gly-gly-OEt = glycylglycine ethyl ester) and [Ir(ptpy)2(gly-gly-gly-OEt)] (3, gly-gly-gly-OEt = glycylglycylglycine ethyl ester) from the reaction of [{Ir(μ-Cl)(ptpy)2}2] (1) with the corresponding peptide ester hydrochlorides in the presence of NaOMe is described. The molecular structure of 2 was confirmed by a single-crystal X-ray diffraction study. The compound crystallized from dichloromethane/iso-hexane in the space group P21/a. In the crystal packing the molecules of 2 exhibit N–H?O hydrogen bonds to the neighbor molecules to form dimeric units. The absorption and emission spectra of 2 and 3 were recorded and exhibit these compounds as strong green-emitting complexes. 相似文献
100.
Flicker K Neuwirth M Strohmeier M Kappes B Tews I Macheroux P 《Journal of molecular biology》2007,374(3):732-748
Pyridoxal 5′-phosphate (PLP) is required as a cofactor by many enzymes. The predominant de novo biosynthetic route is catalyzed by a heteromeric glutamine amidotransferase consisting of the synthase subunit Pdx1 and the glutaminase subunit Pdx2. Previously, Bacillus subtilis PLP synthase was studied by X-ray crystallography and complex assembly had been characterized by isothermal titration calorimetry. The fully assembled PLP synthase complex contains 12 individual Pdx1/Pdx2 glutamine amidotransferase heterodimers. These studies revealed the occurrence of an encounter complex that is tightened in the Michaelis complex when the substrate l-glutamine binds. In this study, we have characterized complex formation of PLP synthase from the malaria-causing human pathogen Plasmodium falciparum using isothermal titration calorimetry. The presence of l-glutamine increases the tightness of the interaction about 30-fold and alters the thermodynamic signature of complex formation. The thermodynamic data are integrated in a 3D homology model of P. falciparum PLP synthase. The negative experimental heat capacity (Cp) describes a protein interface that is dominated by hydrophobic interactions. In the absence of l-glutamine, the experimental Cp is less negative than in its presence, contrasting to the previously characterised bacterial PLP synthase. Thus, while the encounter complexes differ, the Michaelis complexes of plasmodial and bacterial systems have similar characteristics concerning the relative contribution of apolar/polar surface area. In addition, we have verified the role of the N-terminal region of PfPdx1 for complex formation. A “swap mutant” in which the complete αN-helix of plasmodial Pdx1 was exchanged with the corresponding segment from B. subtilis shows cross-binding to B. subtilis Pdx2. The swap mutant also partially elicits glutaminase activity in BsPdx2, demonstrating that formation of the protein complex interface via αN and catalytic activation of the glutaminase are linked processes. 相似文献